ABSTRACT. Bipolar disorder (BD) is characterized by abnormally elevated reward sensitivity and risk taking, that may predispose to hypo/mania. We reported abnormally elevated activation in left ventrolateral prefrontal cortex (vlPFC) during uncertain outcome and reward expectancy in remitted and depressed individuals with BD. The vlPFC encodes the value of different decision-making options. Thus, abnormally elevated left vlPFC activation during uncertain outcome expectancy may reflect heightened representation of the value of decisions that can lead to future reward, ie., heightened reward sensitivity. The role of transcranial direct current stimulation (tDCS) as a treatment for depression is highlighted in an increasing number of studies. In one study, an individual with BDII depression developed hypomania after treatment with anodal (excitatory) tDCS over the left vlPFC. These findings suggest that increased left vlPFC activation in individuals with BD may be a neural mechanism for heightened reward sensitivity, that predisposes to risky decision-making, and, longer term, to risk-taking behaviors and hypo/mania. As a first step toward elucidating these relationships, we wish to determine if left vlPFC cathodal (inhibitory) tDCS reduces left vlPFC activation and functional connectivity (FC) with other reward circuitry regions, e.g., ventral striatum (VS) and amygdala, during uncertain outcome expectancy; and the impact of this intervention on short-term risky decision making. Our specific aims are: 1. In 30, 18-45 year old remitted individuals with BD type I (BDI), and 30 age, gender ratio and IQ-matched healthy control individuals, to compare left vlPFC, VS and amygdala activation and FC during uncertain outcome expectancy, and short-term risky decision-making, and examine across all individuals relationships among neuroimaging measures and short-term risky decision-making; 2. To determine the impact of acute left vlPFC (vs. positive control left somatosensory cortex, SS) cathodal tDCS on these neuroimaging measures and short-term risky decision-making, using individual neuroanatomy-targeted electrode montages; 3. To determine if the impact of this intervention is greater in individuals with BDI than controls, given that in the former, abnormally elevated reward circuitry activation and FC may provide greater capacity for the effect of tDCS upon these measures. We will explore: 1. The effect of acute left vlPFC cathodal tDCS on left vlPFC resting state FC in all participants, and relationships between left vlPFC resting state FC and risky decision making; 2. The relationship between trait impulsive sensation seeking (ISS) and the above neuroimaging and risky decision making measures, and if trait ISS moderates the impact of left vlPFC cathodal tDCS upon these measures across all participants, irrespective of diagnosis. (We previously reported associations between greater trait ISS and greater left vlPFC activation during uncertain outcome expectancy in individuals across different diagnoses). The proposed research will be a first stage toward determining if longer-term left vlPFC cathodal tDCS can ultimately reduce risk for all disorders characterized by risk-taking behaviors.